A. William Pasculle

A large outbreak of Clostridium difficile‐associated disease with an unexpected proportion of deaths and colectomies at a teaching hospital following increased Fluoroquinolone use

BACKGROUND AND OBJECTIVE Fluoroquinolones have not been frequently implicated as a cause of Clostridium difficile outbreaks. Nosocomial C. difficile infections increased from 2.7 to 6.8 cases per 1000 discharges (P < .001). During the first 2 years of the outbreak, there were 253 nosocomial C. difficile infections; of these, 26 resulted in colectomy and 18 resulted in death. We conducted an investigation of a large C. difficile outbreak in our hospital to identify risk factors and characterize the outbreak. METHODS A retrospective case-control study of case-patients with C. difficile infection from January 2000 through April 2001 and control-patients matched by date of hospital admission, type of medical service, and length of stay; an analysis of inpatient antibiotic use; and antibiotic susceptibility testing and molecular subtyping of isolates were performed. RESULTS On logistic regression analysis, clindamycin (odds ratio [OR], 4.8; 95% confidence interval [CI95], 1.9-12.0), ceftriaxone (OR, 5.4; CI95, 1.8-15.8), and levofloxacin (OR, 2.0; CI95, 1.2-3.3) were independently associated with infection. The etiologic fractions for these three agents were 10.0%, 6.7%, and 30.8%, respectively. Fluoroquinolone use increased before the onset of the outbreak (P < .001); 59% of case-patients and 41% of control-patients had received this antibiotic class. The outbreak was polyclonal, although 52% of isolates belonged to two highly related molecular subtypes. CONCLUSIONS Exposure to levofloxacin was an independent risk factor for C. difficile-associated diarrhea and appeared to contribute substantially to the outbreak. Restricted use of levofloxacin and the other implicated antibiotics may be required to control the outbreak

tcdC genotypes associated with severe TcdC truncation in an epidemic clone and other strains of Clostridium difficile

ABSTRACT Severe Clostridium difficile associated disease is associated with outbreaks of the recently described BI/NAP1 epidemic clone. This clone is characterized by an 18-bp deletion in the tcdC gene and increased production of toxins A and B in vitro. TcdC is a putative negative regulator of toxin A&B production. We characterized tcdC genotypes from a collection of C. difficile isolates from a hospital that experienced an outbreak caused by the BI/NAP1 epidemic clone. Sequence analysis of tcdC was performed on DNA samples isolated from 199 toxigenic C. difficile isolates (31% BI/NAP1) from 2001 and 2005. Sequences obtained from 36 (18.6%) isolates predicted wild-type TcdC (232 amino acid residues), whereas 12 (6.1%) isolates had tcdC genotypes with previously described 18- or 39-bp deletions. The remaining isolates comprised 15 unique genotypes. Of these, 5 genotypes contain 18- or 36-bp deletions. Of these five genotypes, one is characterized by a single nucleotide deletion at position 117 resulting in a frameshift that introduces a stop codon at position 196, truncating the predicted TcdC to 65 amino acid residues. All 62 of the isolates in this collection comprising the epidemic clone are characterized by this genotype. This result suggests that severe truncation of TcdC is responsible for the increased toxin production observed in strains belonging to the BI/NAP1 clone and that the 18-bp deletion is probably irrelevant to TcdC function. Further investigations are required to determine the effect of this and other tcdC genotypes on toxin production and clinical disease.

Use of Multilocus Variable Number of Tandem Repeats Analysis Genotyping to Determine the Role of Asymptomatic Carriers in Clostridium difficile Transmission

BACKGROUND Previous studies have suggested that asymptomatic carriers of toxigenic Clostridium difficile are a source of hospital-associated (HA) infections. Multilocus variable number of tandem repeats analysis (MLVA) is a highly discriminatory molecular subtyping tool that helps to determine possible transmission sources. METHODS Clostridium difficile isolates were recovered from perirectal swabs collected for vancomycin-resistant Enterococcus (VRE) surveillance as well as from clinical C. difficile toxin-positive stool samples from July to November 2009 at the University of Pittsburgh Medical Center Presbyterian (UPMC). MLVA was performed to determine the genetic relationships between isolates from asymptomatic carriers and patients with HA C. difficile infection (HA-CDI). Asymptomatic carriage and HA-CDI isolates were considered to be associated if the carriage isolate was collected before the HA-CDI isolate and if the MLVA genotypes had a summed tandem-repeat difference of ≤ 2. RESULTS Of 3006 patients screened, 314 (10.4%) were positive for toxigenic C. difficile, of whom 226 (7.5%) were detected only by VRE surveillance cultures. Of 56 incident cases of CDI classified as HA at UPMC during the study with available isolates, 17 (30%) cases were associated with CDI patients, whereas 16 (29%) cases were associated with carriers. Transmission events from prior bed occupants with CDI (n = 2) or carriers (n = 2) were identified in 4 of 56 cases. CONCLUSIONS In our hospital with an established infection control program designed to contain transmission from symptomatic CDI patients, asymptomatic carriers appear to have played an important role in transmission. Identification and isolation of carriers may be necessary to further reduce transmission of C. difficile in such settings.

Automatic Electronic Laboratory-Based Reporting of Notifiable Infectious Diseases

Electronic laboratory-based reporting, developed by the University of Pittsburgh Medical Center (UPMC) Health System, was evaluated to determine if it could be integrated into the conventional paper-based reporting system. We reviewed reports of 10 infectious diseases from 8 UPMC hospitals that reported to the Allegheny County Health Department in southwestern Pennsylvania during January 1–November 26, 2000. Electronic reports were received a median of 4 days earlier than conventional reports. The completeness of reporting was 74% (95% confidence interval [CI] 66% to 81%) for the electronic laboratory-based reporting and 65% (95% CI 57% to 73%) for the conventional paper-based reporting system (p>0.05). Most reports (88%) missed by electronic laboratory-based reporting were caused by using free text. Automatic reporting was more rapid and as complete as conventional reporting. Using standardized coding and minimizing free text usage will increase the completeness of electronic laboratory-based reporting.

Opportunistic Lung Infection Due to Pittsburgh Pneumonia Agent

Eight immunosuppressed patients had pneumonia due to Pittsburgh Pneumonia Agent (PPA), a gram-negative, weakly acid-fast bacterium cultivatable only in embryonated eggs and guinea pigs and distinct from Legionella pneumophila. The diagnosis was established by isolation of the agent from lung or visualization of the organism in lung tissue. The clinical presentations, radiographic abnormalities and pathology were not specific. The most consistent feature associated with the disease was the recent institution of daily high-dose corticosteriod therapy in all patients. Five of the eight patients died despite broad-spectrum antibiotic and antituberculous therapy. Anti-microbial activity against PPA was demonstrated for sulfamethoxazole combined with trimethoprim, for rifampin and for erythromycin with an egg-protection assay. Serologic studies with an indirect fluorescent-antibody technic suggested that seroconversion or high titers may be a sensitive test for PPA disease. PPA appears to be a newly recognized cause of life-threatening bacterial pneumonia in immunosupressed patients.

Epidemiological Profile of Linezolid-Resistant Coagulase-Negative Staphylococci

BACKGROUND Surveillance studies have shown that <0.1% of coagulase-negative staphylococci are linezolid resistant; however, at our institution, 4% of such organisms were found to be resistant. We investigated the risk factors for and the epidemiological profile of linezolid-resistant coagulase-negative staphylococci. METHODS Susceptibility testing and pulsed-field gel electrophoresis were performed to analyze the genetic relatedness of both linezolid-resistant and linezolid-susceptible isolates. Clinical data were retrieved from medical records, and a case-case-control study was performed to identify unique risk factors for linezolid resistance. RESULTS Isolates recovered from 25 patients with linezolid-resistant coagulase-negative staphylococci were examined; all but 1 of the isolates were identified as Staphylococcus epidermidis, and all but 1 had a minimum inhibitory concentration of linezolid of >256 microg/mL. Pulsed-field gel electrophoresis showed that 21 (84%) of 25 linezolid-resistant isolates exhibited genetic relatedness, whereas linezolid-susceptible isolates were of diverse clones. Unique, independent predictors of linezolid resistance included receipt of linezolid in the 3 months preceding isolation of the coagulase-negative staphylococci (odds ratio, 20.6; 95% confidence interval, 5.8-73.0). CONCLUSION Linezolid-resistant coagulase-negative staphylococci have emerged at our institution and are predominately of a single clone. We believe that the most likely scenario to explain this emergence is that person-to-person spread of linezolid-resistant coagulase-negative staphylococci led to establishment of skin colonization with the strain. Subsequent use of linezolid was followed by selection of the linezolid-resistant strain, which then became the dominant skin flora. The potential for a parallel scenario involving clonal dissemination followed by selection of linezolid-resistant methicillin-resistant Staphylococcus aureus is a real possibility.

Extragenital Mycoplasma hominis infections in adults

PURPOSE To heighten awareness of the role of Mycoplasma hominis as an extragenital pathogen in adults. PATIENTS AND METHODS AND RESULTS Patients ranged in age from 14 to 76 years. Thirteen patients were immunosuppressed, including nine organ transplant recipients; three were receiving steroids, and two had an underlying malignancy. The remainder were immunocompetent. Thirteen patients had prior surgery at or near the site of infection. M. hominis was isolated from normally sterile sites such as blood or cerebrospinal, pleural, abdominal and joint fluids, and bone. Non-sterile sites of isolation included surgical wounds and pulmonary secretions. The organism was detected in anaerobic cultures of clinical specimens sent to the laboratory for routine bacteriologic culture. Gram stains of fluids or wound drainage revealed neutrophils but no bacteria. Anti-mycoplasmal therapy was effective in eradicating the organism in 13 of 15 patients who were treated. Of those in whom treatment failed, one patient had an antibiotic-resistant isolate and the other had M. hominis isolated from the lung at postmortem after just 2 days of therapy. CONCLUSION Our experience suggests that significant infections due to M. hominis, although uncommon, are not rare, and methods to isolate and identify this organism should be available for general adult medical and surgical populations.

High mortality rates among solid organ transplant recipients infected with extensively drug-resistant Acinetobacter baumannii: using in vitro antibiotic combination testing to identify the combination of a carbapenem and colistin as an effective treatment regimen ☆ ☆☆ ★

Extensively drug-resistant (XDR) Acinetobacter baumannii infections caused 91% (10/11) mortality in transplant recipients. Isolates were colistin-susceptible initially, but susceptibility decreased during therapy in 40% (4/10). We tested antibiotic combinations against XDR Acinetobacter in vitro and demonstrated positive interactions for carbapenem-colistin. Subsequently, 80% (4/5) of transplant patients were treated successfully with carbepenem-colistin regimens.

SHV-Type Extended-Spectrum Beta-Lactamase Production Is Associated with Reduced Cefepime Susceptibility in Enterobacter cloacae

ABSTRACT Cefepime is a potentially useful antibiotic for treatment of infections with Enterobacter cloacae. However, in our institution the MIC90 for E. cloacae bloodstream isolates is 16 μg/ml. PCR amplification of bla genes revealed that one-third (15/45) of E. cloacae bloodstream isolates produced SHV-type extended-spectrum beta-lactamases (ESBLs) in addition to hyperproduction of AmpC-type beta-lactamases. The majority (11/15) of ESBL producers also produced the TEM-1 beta-lactamase. The SHV types included SHV-2, -5, -7, -12, -14, and -30. All but two of the ESBL-producing E. cloacae isolates, but none of the non-ESBL-producing strains, had MICs of cefepime of ≥2 μg/ml. The MIC90 for cefepime for ESBL-producing strains was 64 μg/ml, while for non-ESBL producers it was 0.5 μg/ml. Using current Clinical and Laboratory Standards Institute breakpoints for cefepime, two thirds (10/15) of ESBL-producing isolates would have been regarded as susceptible to cefepime. Phenotypic ESBL detection methods were generally unreliable with these E. cloacae isolates. Based on these results, pharmacokinetic, pharmacodynamic, and clinical reevaluation of cefepime breakpoints for E. cloacae may be prudent.

Determination of risk factors associated with isolation of linezolid-resistant strains of vancomycin-resistant Enterococcus.

OBJECTIVE To identify independent risk factors associated with isolation of linezolid-resistant, vancomycin-resistant Enterococcus (VRE). DESIGN A retrospective, case-case-control study. SETTING A tertiary care, academic medical center.Methods. VRE isolates from clinical cultures were retrospectively analyzed for linezolid resistance during our 18-month study period. Clinical data were obtained from electronic patient records, and the risk factors associated with isolation of linezolid-resistant VRE were determined by comparison of 2 case groups with a control group. RESULTS A total of 20% of the VRE isolates analyzed during the study period were linezolid resistant, and resistant isolates were most commonly recovered from the urine (40% of resistant isolates). Risk factors found to be associated with isolation of linezolid-resistant VRE were peripheral vascular disease and/or the receipt of a solid organ transplant, total parenteral nutrition, piperacillin-tazobactam, and/or cefepime. Only 25% of patients from whom linezolid-resistant VRE was isolated had previous linezolid exposure, and in the multivariate model this was not found to be a risk factor associated with the isolation of linezolid-resistant VRE. CONCLUSIONS The results of this analysis suggest that there is horizontal transmission of linezolid-resistant VRE in our institution and highlight the need for improved infection control measures. Furthermore, the high incidence of linezolid-resistant VRE demands a reassessment of our empirical antibiotic selection for patients infected with VRE.